Acromegalic patients have continued to be followed with respect to pituitary irradiation. Further, we are evaluating the effects of transphenoidal hypophysectomy in these patients and comparing them to the pituitary-irradiated patients. When bromocryptine was used as an adjunct or as primary therapy for acromegaly, it was found that approximately one-third of the patients had some reduction in growth hormone concentration but there was no alteration in the form of the growth hormone components in circulating blood. Recently, human growth hormone has been cross-linked to its specific cellular receptor on IM-9 cultured lymphocytes. Under reducing conditions the predominant band is an approximate 140K protein. Under non-reducing conditions, however, a molecular weight component greater than 200K is observed. Whether this represents an oligomer of the reduced peptide is uncertain at this point. Further attempts were made to see if the growth hormone receptor was a protein kinase or a substrate for that kinase activity, it does not. Thus, the growth hormone receptor is not analogous to the insulin receptor. The heterogeneity of circulating growth hormone in plasma has been studied. Pituitary growth hormone was injected in normal volunteers and the individual growth hormone components isolated by gel filtration. It was found that the half-time of the "little" (22,000 Da) growth hormone component was faster than the "big" and the "pre-big" growth hormone components, respectively. This is compatible with a receptor-mediated type of removal of these components since previous studies have shown that the high molecular weight forms have lower radioreceptor activity than the 22,000 growth hormone preparation.